Reovirus outer capsid protein micro1 induces apoptosis and associates with lipid droplets, endoplasmic reticulum, and

Caroline M Coffey1, Alexander Sheh, Irene S Kim

  • 1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.

Journal of Virology
|August 17, 2006
PubMed

Insights

Mammalian reovirus micro1 protein alone induces apoptosis in cells. Its interaction with intracellular membranes and sigma3 protein regulates this cell death process during infection.

Area of Science:

  • Virology
  • Cell Biology
  • Molecular Biology

Background:

  • Mechanisms of reovirus-induced apoptosis are not fully understood.
  • Mammalian reovirus S1 and M2 genes were previously linked to apoptosis induction.
  • Previous studies lacked direct evidence of gene products inducing apoptosis independently.

Purpose of the Study:

  • To investigate the direct apoptotic capacity of mammalian reovirus M2 gene product, micro1.
  • To determine the cellular localization and functional domains of micro1 in apoptosis induction.
  • To examine the regulatory role of sigma3 protein in micro1-mediated apoptosis.

Main Methods:

  • Transfection of cells with micro1-expressing constructs.
  • Microscopy to determine micro1 localization in transfected and infected cells.
  • Co-expression experiments with sigma3 to assess its effect on micro1 function.

Main Results:

  • Mammalian reovirus micro1 protein alone induced apoptosis in transfected cells.
  • Micro1 localized to lipid droplets, endoplasmic reticulum, and mitochondria.
  • Specific alpha-helical regions in micro1 were crucial for apoptosis induction and membrane association; co-expression with sigma3 abrogated these effects.

Conclusions:

  • Micro1 protein directly induces apoptosis, potentially through association with intracellular membranes.
  • The interaction of micro1 with lipid droplets, ER, and mitochondria is critical for its apoptotic function.
  • Sigma3 protein may regulate micro1-mediated apoptosis during reovirus infection.

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